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基于网络药理学探讨络风宁3号方治疗心律失常的作用机制

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摘要:

目的 基于网络药理学预测络风宁3号方治疗心律失常的分子作用途径。方法 通过中药系
统药理学数据库(TCMSP数据库)、ETCM数据库、DrugBank数据库检索络风宁3号方有效成分及作用靶
点;其次使用Genecards数据库检索心律失常发病相关靶点,利用CytoScape3.7.2软件构建药物-有效成分-
靶点基因网络;分别通过STRING和DAVID数据库,对交集靶点进行PPI分析和GO、KEGG富集分析。结
果 共得到络风宁3号方中有效成分120个、有效成分所对应的药物靶点239个、与心律失常相关的基因靶
点1091个;两组靶点相互映射,最终得到交集靶点82个、关键靶点10个、KEGG通路116条。络风宁3号
方中槲皮素、β-谷甾醇、山奈酚、汉黄芩素等主要有效成分可能通过作用于白细胞介素-6(IL-6)、
血管内皮生长因子A (VEGFA)、蛋白激酶B1(AKT1)、肿瘤坏死因子(TNF)、基质金属蛋白酶9
(MMP9)等靶标因子,调节磷脂酰肌醇3-激酶(PI3K-Akt)信号通路、TNF信号通路、丝裂原激活蛋
白激酶(MAPK)信号通路、Toll样受体(TLR)信号通路、缺氧诱导因子1(HIF-1)信号通路等,发挥
抗炎、抗氧化应激、调节离子通道等作用,治疗心律失常。结论 络风宁3号方可能通过抗炎,抗氧化应
激等多靶点、多通道起到治疗心律失常作用,为后续临床和基础研究提供理论依据。

Abstract:

Objective To predict the molecular function pathway of Luofengning Granules Ⅲ in treating
arrhythmia based on network pharmacology. Methods Firstly, the effective components and targets of Luofengning
Granules Ⅲ were retrieved in TCMSP database, ETCM database and DrugBank database. Secondly, Genecards
database was used to retrieve targets related to arrhythmia, and Cytoscape 3.7.2 software was used to construct
medicinal-active ingredient-target gene network. Finally, PPI analysis and enrichment analyses of GO and KEGG
were performed on the intersecting targets through STRING and DAVID databases. Results A total of 120 effective
components, 239 drug targets and 1091 gene targets related to arrhythmia were obtained from Luofengning Granules
Ⅲ, and 2 groups of targets were mapped to each other. Finally, 82 intersection targets, 10 key targets and 116 KEGG
pathways were obtained. The main active ingredients in Luofengning Granules Ⅲ, such as quercetin, β-sitosterol,
kaempferol, and wogonin probably played the roles of anti-inflammatory, anti-oxidative stress, and regulating ion
channels to treat arrhythmia through effecting on target factors including interleukin-6 (IL6), vascular endothelial
growth factor A (VEGFA), protein kinase B1 (AKT1), tumor necrosis factor (TNF) and matrix metalloproteinase 9
(MMP9), and regulating some signaling pathways including phosphatidylinositol 3-kinase (PI3K-Akt), TNF, mitogen
activated protein kinase (MAPK), Toll-like receptor (TLR) and hypoxia-inducible factor 1 (HIF-1). Conclusion
Luofengning Granules Ⅲ can treat arrhythmia through multi-targets and multi-channels of anti-inflammatory and
anti-oxidative stress, which provides a theoretical basis for the follow-up clinical and basic researches.

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参考文献:

  • 2008

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